Kai Chen

Background: GATA-binding protein 3 (GATA3) is a pivotal transcriptional regulator during mammary gland development and serves as a core biomarker in breast cancer. Although traditionally recognized for maintaining luminal differentiation, its high mutation frequency reveals a complex, dual role in tumorigenesis. Methods: This review summarizes the multidimensional roles of GATA3, with an emphasis on molecular regulatory networks, clinical diagnostic applications, and significance in therapeutic response in the field of breast cancer. Results: At the molecular level, GATA3 operates within a core transcriptional regulatory network, synergistically interacting with key factors like ERα and FOXA1 to govern the luminal phenotype. Clinically, GATA3 serves as a highly sensitive core biomarker for distinguishing between primary and metastatic breast cancer. Notably, emerging biomarkers like TRPS1 and SOX10 provide essential complementary value in the diagnosis of triple-negative breast cancer. High expression of GATA3 strongly correlates with a favorable prognosis and sensitivity to endocrine therapy. Conversely, downregulated GATA3 expression enhances tumor aggressiveness, increases sensitivity to certain chemotherapeutic agents such as anthracyclines, and promotes the formation of responsive “hot” microenvironment. Furthermore, although GATA3 mutations are relatively common among patients with breast cancer, their clinical and prognostic significance warrants further in-depth investigation. Conclusion: As a core regulator of breast cancer cell plasticity and the tumor microenvironment, GATA3 extends far beyond its traditional role as a luminal biomarker. Elucidating its multidimensional roles and exploring its emerging therapeutic potential will continue to propel the field of breast cancer toward more sophisticated and personalized diagnostic and therapeutic paradigms.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide, characterized by persistently high and increasing rates of incidence, recurrence and mortality, thereby posing a considerable global public health challenge. Within the complex molecular network driving the malignant progression of HNSCC, Dickkopf‑1 (DKK1), a classical secreted antagonist of the Wnt signaling pathway, has garnered considerable attention due to its pleiotropic roles in tumor initiation, progression and therapeutic resistance. The expression of DKK1 is regulated by a sophisticated network involving both canonical and non‑canonical Wnt pathways, and it exhibits high spatiotemporal specificity and context dependency. The present narrative review discusses the regulatory mechanisms underlying DKK1 expression, its prognostic significance in HNSCC, pro‑tumorigenic molecular mechanisms, immunomodulatory functions and its clinical translational potential as a biomarker and therapeutic target. The present review aims to provide novel insights into the pathogenesis of HNSCC and establish a theoretical foundation for advancing DKK1‑based precision diagnostics and therapeutic strategies.

Epstein-Barr virus (EBV) is a ubiquitous oncogenic virus linked to malignancies and autoimmune diseases. No licensed vaccines are currently available. Recent advances in EBV biology have enabled rational antigen selection and accelerated development of multivalent vaccines using platforms such as mRNA and nanoparticles. This review outlines key mechanisms, vaccine targets, and platform innovations, and discusses major challenges and future directions for EBV vaccine development.

BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide, ranking third in United States regarding incidence and mortality. Notably, approximately 40% of colon cancer cases harbor oncogenic KRAS mutations, resulting in the continuous activation of epidermal growth factor receptor signaling. AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance. METHODS Weighted gene co-expression network analysis, in combination with additional bioinformatics analysis, were conducted to screen the key factors driving the progression of KRAS mutant colon cancer. Meanwhile, various in vitro experiments were also conducted to explore the biological function of transglutaminase 2 (TGM2). RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival. Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer. Additionally, biological roles of the key gene TGM2 was also assessed, suggesting that the downregulation of TGM2 attenuated the proliferation, invasion, and migration of the KRAS mutant colon cancer cell line. CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer. This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

Adipocyte is a unique and versatile component of bone marrow microenvironment (BMM). However, the dynamic evolution of Bone Marrow (BM) adipocytes from the diagnosis of B cell Acute Lymphoblastic Leukemia (B-ALL) to the post-treatment state, and how they affect the progression of leukemia, remains inadequately explicated. Primary patient-derived xenograft models (PDXs) and stromal cell co-culture system are employed in this study. We show that the dynamic evolution of BM adipocytes from initial diagnosis of B-ALL to the post-chemotherapy phase, transitioning from cellular depletion in the initial leukemia niche to a fully restored state upon remission. Increased BM adipocytes retards engraftment of B-ALL cells in PDX models and inhibits cells growth of B-ALL in vitro. Mechanistically, the proliferation arrest of B-ALL cells in the context of adipocytes-enrichment niche, might attribute to the presence of adiponectin secreted by adipocytes themselves and the absence of cytokines secreted by mesenchymal stem cell (MSCs). In summary, our findings offer a novel perspective for further in-depth understanding of the dynamic balance between BMM and B-ALL.

Observational and Mendelian randomization (MR) studies have established links between dyslipidemia and select cancer susceptibilities. However, there is a lack of comprehensive exploration of causal relationships spanning diverse cancer types. Here, we conducted a two-sample MR analysis to elucidate the causative connections between 9 blood lipid metabolic profiles (namely, adiponectin, leptin, lipoprotein A, apolipoprotein A1, apolipoprotein B, cholesterol, triglycerides, LDL-cholesterol, and HDL-cholesterol) and 21 site-specific cancer risks. Our findings reveal genetically predicted adiponectin levels to be associated with a reduced ovarian cancer risk, while genetically determined leptin increases bladder cancer risk but decreases prostate cancer risk. Lipoprotein A elevates risk of prostate cancer while diminishing risk of endometrial cancer, while apolipoprotein A1 heightens risks of breast and cervical cancers. Furthermore, elevated levels of cholesterol are positively correlated with kidney cancer, and triglycerides demonstrate a positive association with non-melanoma skin cancer but a negative association with breast cancer. Protective effects of genetically predicted LDL-cholesterol on endometrial cancer and adverse effects of HDL-cholesterol on breast cancer are also observed. Our study conclusively establishes that blood lipid metabolic profiles exert causal effects on cancer susceptibility, providing more robust evidence for cancer prevention and prompting contemplation regarding the future health of the human populace.

BackgroundDickkopf-1 (DKK1) exhibits abnormal expression in various cancers and correlates with poor prognosis. This study investigates DKK1's prognostic relevance in head and neck squamous cell carcinoma (HNSC).MethodsWe conducted a comprehensive search across literature and sequencing databases to gather eligible studies and HNSC datasets. We calculated pooled standardized mean differences (SMD) and 95% confidence intervals (CI) for clinical characteristics, as well as hazard ratios (HR) with 95% CIs for overall survival (OS) and progression-free/disease-free survival (PFS/DFS). Sensitivity analysis gauged result stability, and Egger's test assessed publication bias.ResultsPooled results indicated that HNSC patients with higher T-stage exhibited elevated DKK1 expression levels, and this elevated expression was associated with shorter OS and PFS/DFS. While sensitivity analysis identified some studies significantly affecting pooled results, most were unaffected, and no publication bias was detected.ConclusionDKK1 holds promise as a potential biomarker for predicting poor prognosis in HNSC patients, but further research is needed for confirmation.

Acute myeloid leukemia (AML) is a heterogeneous myeloid neoplasm with poor clinical outcome, despite the great progress in treatment in recent years. The selective Bcl-2 inhibitor venetoclax (ABT-199) in combination therapy has been approved for the treatment of newly diagnosed AML patients who are ineligible for intensive chemotherapy, but resistance can be acquired through the upregulation of alternative antiapoptotic proteins. Here, we reported that a newly emerged histone deacetylase inhibitor, chidamide (CS055), at low-cytotoxicity dose enhanced the anti-AML activity of ABT-199, while sparing normal hematopoietic progenitor cells. Moreover, we also found that chidamide showed a superior resensitization effect than romidepsin in potentiation of ABT-199 lethality. Inhibition of multiple HDACs rather than some single component might be required. The combination therapy was also effective in primary AML blasts and stem/progenitor cells regardless of disease status and genetic aberrance, as well as in a patient-derived xenograft model carrying FLT3-ITD mutation. Mechanistically, CS055 promoted leukemia suppression through DNA double-strand break and altered unbalance of anti- and pro-apoptotic proteins (e.g., Mcl-1 and Bcl-xL downregulation, and Bim upregulation). Taken together, these results show the high therapeutic potential of ABT-199/CS055 combination in AML treatment, representing a potent and alternative salvage therapy for the treatment of relapsed and refractory patients with AML.